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(12) Patent Application Publication (10) Pub. No.: US 2015/0038576A1 Timokhina Et Al

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(12) Patent Application Publication (10) Pub. No.: US 2015/0038576A1 Timokhina Et Al US 20150.038576A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2015/0038576A1 Timokhina et al. (43) Pub. Date: Feb. 5, 2015 (54) COMPOSITIONS AND THEIR USE FOR A24F 47/00 (2006.01) SMOKING CESSATION AND OTHER A63L/2 (2006.01) TREATMENTS A63L/II (2006.01) (71) Applicant: SENTIENS, LLC, Charlotte, NC (US) A6M I5/00 (2006.01) A63L/25 (2006.01) (72) Inventors: Inna S. Timokhina, Potomac, MD (US); A63L/343 (2006.01) Reid von Borstel, Potomac, MD (US); (52) U.S. Cl DennisMSG Tan, Weddington,NEW, NC 'S(US): CPCAV e. we............... A24B 15/16 (2013.01); A61 K3I/125 s s (2013.01); A61 K3I/05 (2013.01); A61 K (73) Assignee: SENTIENS, LLC, Charlotte, NC (US) 3 1/343 (2013.01); A61 K31/12 (2013.01); A6 IK3I/II (2013.01); A61M 15/009 (21) Appl. No.: 14/449,533 (2013.01); A24F 47/008 (2013.01) USPC ........... 514/470; 13 1/270; 13 1/273: 514/692; (22) Filed: Aug. 1, 2014 514/731: 514/678; 514/701: 128/200.14; 128/202.21 Related U.S. Application Data (60) Provisional application No. 61/861,865, filed on Aug. 2, 2013. (57) ABSTRACT Publication Classification A composition includes a liquid. The liquid aerosolizes for (51) Int. Cl. delivery to a user by an airway. The liquid includes an agent A24B 15/16 (2006.01) that activates a TRPV3 channel. The agent includes a terpe A6 IK3I/05 (2006.01) noid compound. Patent Application Publication Feb. 5, 2015 US 2015/0038576 A1 covC s US 2015/0038576 A1 Feb. 5, 2015 COMPOSITIONS AND THEIR USE FOR channels, expressed in sensory neurons of the respiratory SMOKING CESSATION AND OTHER tract. In some embodiments, an apparatus takes the form of a TREATMENTS cigarette Substitute device for alleviating cigarette craving or Supporting Smoking cessation. The cigarette Substitute device CROSS-REFERENCE TO RELATED may include Such devices as electronic cigarettes, non-elec APPLICATIONS tronic cigarette Substitute devices with or without heating 0001. This application claims priority to U.S. Provisional elements, inhalers, vaporizers, and any other device that may App. Ser. No. 61/861,865, filed Aug. 2, 2013, which is hereby deliver the composition to the airway. incorporated by reference in its entirety. 0010. In the following discussion, cigarette smoking is used as a generic and illustrative term to include cigarette, BACKGROUND cigar or pipe Smoking without loss of generality to Smoking in general. 0002 Chronic exposure to cigarette Smoke can lead to 0011 Embodiments of the disclosure provide composi inflammatory airway conditions, such as COPD, and tobacco tions of bioactive plant derived compounds, which may be Smoking can cause cancer and respiratory and cardiovascular nicotine and tobacco free. Embodiments of the disclosure disease. These negative health effects can be attributed to the further provide methods and devices for delivering the com carcinogenic, oxidant and other toxic constituents of cigarette positions to the respiratory tracts of smokers, former Smokers smoke. It has been estimated that up to 50% of heavy smokers or other subjects, using vaporizing devices. The constituents develop chronic obstructive pulmonary disease (COPD), of the compositions may possess anti-inflammatory, anti while prevalence of COPD in general population is estimated oxidant and/or anti-anxiety activities. The compositions, as 10%. Chronic obstructive pulmonary disease (COPD) is methods and devices provide improved mimicry of Smoking now recognized as a leading cause of morbidity and mortality and Suppress Smoking abstinence symptoms. worldwide and is associated with significant individual and 0012 Mechanisms of neurogenic and tissue inflammation socioeconomic burden. Furthermore, COPD patients can in the respiratory tract induced by cigarette Smoke will now have high levels of anxiety and depression, which are related be discussed. Chemical irritants are detected by chemosensi to progressive worsening of the disease. Exposure to tobacco tive C-fibers—e.g. sensory neurons that extend numerous Smoke is a significant etiologic agent of this disease, which is terminals Superficially into the airway epithelium, placing characterized by progressive airflow limitation with an abnor them in an ideal position to react to inhaled irritants. These mal inflammatory response in the Small airways and alveoli, neurons express chemosensory TRP receptors, including Small airway remodeling, chronic bronchitis, pulmonary TRPA1, TRPV1, TRPV3 and TRPM8. The TRPA1 receptor hypertension and emphysema. The inflammation induced by is abroad spectrum sensor for irritants due to its structure, and cigarette Smoke can lead to an increase in protease produc it plays an important role in sensing noxious tobacco Smoke tion, a major contributor to lung destruction, seen in emphy constituents. Furthermore, TRPA1 mediates neurogenic sema. Other factors contributing to the development of COPD inflammation of sensory nerves induced by unsaturated alde include exposure to dusts, fumes and air pollution particles. hyde components of cigarette Smoke Such as acrolein and crotonaldehyde. TRPA1 is also a sensor for multiple oxidants BRIEF SUMMARY contained in cigarette Smoke. 0003. In an embodiment, a composition includes a liquid. 0013 Transient sensitization of airway neurons by ciga The liquid aerosolizes for deliver to a user by an airway. The rette Smoke or chemical irritants contributes to airway pro liquid includes an agent that activates a TRPV3 channel. The tection, eliminating these irritants from the respiratory tract agent includes a terpenoid compound. and promoting tissue healing and recovery. In contrast, per 0004. In another embodiment, a device includes a liquid sistent neuronal sensitization by cigarette Smoke in habitual and a housing. The liquid aerosolizes for deliver to a user by Smokers may lead to respiratory irritation and neurogenic an airway. The liquid includes an agent that activates a inflammation in a TRPA1 dependent manner. Inflamed nerves TRPV3 channel. The agent includes a terpenoid compound. secrete pro-inflammatory neuropeptides induced by toxic and The housing delivers the liquid aerosolized to the user. oxidant components of cigarette Smoke thereby further pro moting tissue inflammation and damage. Thus, neuronal BRIEF DESCRIPTION OF THE DRAWINGS inflammation occurring in parallel with airway tissue inflam 0005 FIG. 1 is a perspective view of an exemplary device mation can lead to development of inflammatory airway con for delivering constituents of the present disclosure. ditions, such as COPD and asthma. 0014 Mechanisms of chronic conditions of itch and cough 0006 FIG. 2 is a perspective view of an exemplary inhaler induced by cigarette smoke will now be discussed. Multiple device for delivering constituents of the present disclosure. TRPA1 activators, particularly cigarette Smoke, evoke cough 0007 FIG. 3 is an exploded schematic side view of an in animals and humans. TRPA1 may act as a mediator of exemplary device for delivering constituents of the present histamine independentitch. Oxidants cause itch and resulting disclosure. scratching behavior in a TRPA1 dependent manner. Oxida tive stress is indicative of most acute and chronic inflamma DETAILED DESCRIPTION tory airway conditions. Reactive oxygen species (ROS) are 0008 Embodiments described herein relate generally to a generated by infiltrating macrophages and neutrophils during composition, methods and devices for delivering the compo inflammation. Thus, itch and cough may be induced both by sition, that exhibit properties of the present disclosure. toxic and oxidant constituents of cigarette Smoke and by 0009. The present disclosure is generally directed to com endogenous inflammatory mediators released by inflamed positions, apparatuses and methods for delivering composi tissues in the respiratory tract of heavy Smokers. Continuous tions that act on transient receptor potential V3 (TRPV3) exposure of airway tissues to this “inflammatory Soup' may US 2015/0038576 A1 Feb. 5, 2015 provide a basis for progressive worsening of the disease, cant functional impairment and pose risk factors for numer which may be observed in COPD and asthma, as well as ous additional diseases. Thus, Suppressing anxiety associated reactive respiratory tract syndrome (RADS). These inflam with withdrawal from Smoking addiction may be an impor matory airway conditions may be considered diseases of tant factor for increasing Smoke cessation rates and reducing chemical sensing. negative side effects of withdrawal. 00.15 Despite well-known adverse health consequences 0021 Nicotine replacement therapy medications can of smoking, approximately 20% of U.S. adults smoke increase quit rates an average 1.4 times compared to placebo. tobacco cigarettes. This number is higher in other countries. However, even with the use of medications, the success rate of Quitting smoking is difficult because of the aversive with quitting remains low. The percentage of Smokers who relapse drawal symptoms that accompany tobacco abstinence. Symp within six months with the use of nicotine replacement thera toms of tobacco abstinence include physical complaints such pies is reported to be 93%. Although many nicotine replace as headache and hunger, negative mood and high irritability, ment therapies products have been available in the US during decrease in attention and cognitive function, and increased the past decade, the overall quit rate has changed very little, cigarette craving and Smoking urges. from 48.7% in 1998 to 51.1% in 2008. Furthermore, many 0016. Inflammatory “throatitch'
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